3-[(4-methyl-6-phenyl-pyrimidin-2-ylamino)methyl]benzoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-[(4-methyl-6-phenyl-pyrimidin-2-ylamino)methyl]benzoic acid
• 英文别名: 3-[[(4-Methyl-6-phenylpyrimidin-2-yl)amino]methyl]benzoic acid；3-[[(4-methyl-6-phenylpyrimidin-2-yl)amino]methyl]benzoic acid
• 化学式: C₁₉H₁₇N₃O₂
• 分子量: 319.363
• InChiKey: AIZLHGMLYMRNNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  75.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.25h， 生成 3-[(4-methyl-6-phenyl-pyrimidin-2-ylamino)methyl]benzoic acid
  参考文献：
  名称：

  Discovery of 2-(Cyclohexylmethylamino)pyrimidines as a New Class of Reversible Valosine Containing Protein Inhibitors

  摘要：

  Valosine-containing protein (VCP), also known as p97 or cdc48 in yeast, is a highly abundant protein belonging to the AAA ATPase family involved in a number of essential cellular functions, including ubiquitin-proteasome mediated protein degradation, Golgi reassembly, transcription activation, and cell cycle control. Altered expression of VCP has been detected in many cancer types sometimes associated with poor prognosis. Furthermore, VCP mutations are causative of some neurodegenerative disorders. In this paper we report the discovery, synthesis, and structure-activity relationships of substituted 2-aminopyrimidines, representing a new class of reversible VCP inhibitors. This class of compounds, identified in a HTS campaign against recombinant VCP, has been progressively expanded and manipulated to increase biochemical potency and gain cellular activity.

  DOI：

  10.1021/jm501313x

文献信息

• Discovery of 2-(Cyclohexylmethylamino)pyrimidines as a New Class of Reversible Valosine Containing Protein Inhibitors
  作者：Giovanni Cervi、Paola Magnaghi、Daniela Asa、Nilla Avanzi、Alessandra Badari、Daniela Borghi、Michele Caruso、Alessandra Cirla、Liviana Cozzi、Eduard Felder、Arturo Galvani、Fabio Gasparri、Antonio Lomolino、Steven Magnuson、Beatrice Malgesini、Ilaria Motto、Maurizio Pasi、Simona Rizzi、Barbara Salom、Graziella Sorrentino、Sonia Troiani、Barbara Valsasina、Thomas O’Brien、Antonella Isacchi、Daniele Donati、Roberto D’Alessio

  DOI：10.1021/jm501313x

  日期：2014.12.26

  Valosine-containing protein (VCP), also known as p97 or cdc48 in yeast, is a highly abundant protein belonging to the AAA ATPase family involved in a number of essential cellular functions, including ubiquitin-proteasome mediated protein degradation, Golgi reassembly, transcription activation, and cell cycle control. Altered expression of VCP has been detected in many cancer types sometimes associated with poor prognosis. Furthermore, VCP mutations are causative of some neurodegenerative disorders. In this paper we report the discovery, synthesis, and structure-activity relationships of substituted 2-aminopyrimidines, representing a new class of reversible VCP inhibitors. This class of compounds, identified in a HTS campaign against recombinant VCP, has been progressively expanded and manipulated to increase biochemical potency and gain cellular activity.